Immune Responses Against Native and Chemically Modified Albumins in Mice

Abstract

Abstract Albumin antigens were chemically modified at their charged residues by various means (i.e., methylation, acetylation, succinylation) and the effect of the modification reactions on humoral and cellular immune responses was compared. The modifications resulted in profound changes of the molecules' physicochemical properties (charge, conformation, state of aggregation) and in a destruction of the majority of serologically detectable native albumin determinants. On the level of the humoral antibody response the effects of the modifications were i) pronounced reduction of the response against native determinants and ii) induction of an antibody response against new antigenic determinants (NAD) on the modified proteins. Helper (T) lymphocyte responses as a test for cellular immunity were investigated in cell transfer experiments. When using limiting doses of immunogen for primary immunization, it could be shown that none of the modification reactions had any negative impact on the capacity of the albumin to induce helper cells reacting with the native albumin. In the same experiments, however, a marked reduction on the level of albumin-specific antibody-forming cell precursors (B cells) was observed. These results suggest that there are different structural requirements for the induction of B and T cell responses against native protein antigens. Compared to antibodies, helper cells induced by differently modified albumins seemed to have a higher degree of cross-reactivity. However, they also revealed a notable discriminating capacity, suggesting that both antibodies and helper cells were able to distinguish on the modified proteins NAD from native determinants. Possible interpretations of the results are discussed.